Abstract：
Colorectal cancer (CRC) ranks as the third most prevalent cancer type globally. Nevertheless, the fundamental mechanisms driving CRC progression remain ambiguous, and the prognosis for the majority of patients diagnosed at an advanced stage is dismal. YWHA/14-3-3 proteins serve as central nodes in several signaling pathways and are closely related to tumorigenesis and progression. However, their exact roles in CRC are still poorly elucidated. In this study, we revealed that YWHAG was the most significantly upregulated member of the YWHA/14-3-3 family in CRC tissues and was associated with a poor prognosis. Subsequent phenotypic experiments showed that YWHAG promoted the proliferation, migration, and invasion of CRC cells. Mechanistically, RNA-seq data showed that multiple signaling pathways, including Wnt and epithelial-mesenchymal transition, were potentially regulated by YWHAG. CTTN was identified as a YWHAG-associated protein, and mediated its tumor-promoting functions by activating the Wnt/β-catenin signaling in CRC cells. In summary, our data indicate that YWHAG facilitates the proliferation, migration, and invasion of CRC cells by modulating the CTTN-Wnt/β-catenin signaling pathway, which offers a novel perspective for the treatment of CRC.
摘要：
结直肠癌（CRC）在全球范围内排名第三。然而，推动CRC进展的基本机制仍然模棱两可，大多数诊断为晚期的患者的预后令人沮丧。YWHA/14-3-3蛋白是几种信号通路的中心节点，与肿瘤发生和发展密切相关。然而,它们在CRC中的确切作用尚不清楚.在这项研究中,我们发现YWHAG是CRC组织中YWHA/14-3-3家族中最显著上调的成员,并且与不良预后相关.随后的表型实验表明，YWHAG促进增殖，迁移,和CRC细胞的侵袭。机械上,RNA-seq数据显示，多个信号通路，包括Wnt和上皮间质转化，可能受到YWHAG的调控。CTTN被鉴定为YWHAG相关蛋白，并通过激活CRC细胞中的Wnt/β-catenin信号传导来介导其促肿瘤功能。总之,我们的数据表明YWHAG促进了增殖，迁移,通过调节CTTN-Wnt/β-catenin信号通路,这为CRC的治疗提供了新的视角。
